A modified polyimide hollow fiber membrane and its application

Abstract

The present invention discloses a modified polyimide hollow fiber membrane. The hollow fiber membrane comprises a polysulfone / polyethersulfone matrix component and a modified polyimide hydrophobic polymer containing 30% to 100% of the matrix component by weight. The modified polyimide hydrophobic polymer is prepared by mixing water, a strongly polar solvent, an alkaline catalyst, and a polyimide resin at 80 to 120°C for a partial hydrolysis reaction for 5 to 10 hours. After the solution is cooled, the pH is adjusted to 1 to 3 to remove water. A polyamine is first added and stirred for 2 to 4 hours. A carboxyl-containing anticoagulant is then added and a grafting reaction is carried out for 12 to 48 hours to obtain the modified polyimide hydrophobic polymer. The hollow fiber membrane prepared by the present invention has a good ultrafiltration coefficient, significantly improved hydrophilicity, effectively reduces the deposition of prothrombin and fibrin, and significantly improves the anticoagulant effect, making it suitable for use as a blood purification material.

Description

Technical Field

[0001] The present invention relates to the field of biomaterials, and in particular to a modified polyimide hollow fiber membrane and applications thereof. Background Art

[0002] Polysulfone / polyethersulfone is a polymer material with excellent overall performance, including excellent heat resistance, physical and mechanical properties, insulation properties, and relatively good biocompatibility. It has been widely used in many fields. Polysulfone / polyethersulfone also has excellent membrane-forming and filtration properties, making it one of the most common materials for preparing hollow fiber membranes.

[0003] Existing polysulfone resins, such as those in CN113214484A and CN111420563A, which are composites of polyimide, polyurethane, and other materials, have significantly improved permeability to water molecules and are often used in water treatment applications such as seawater / brackish water desalination, where inorganic substances are predominant. However, when applied clinically in contact with blood, polysulfone / polyethersulfone membranes exhibit strong hydrophobicity and the sulfur and oxygen atoms in their structure have strong polarity, resulting in strong adhesion to platelets. Furthermore, the porous structure of the fiber membranes facilitates the deposition of prothrombin and fibrin in the membrane pores, thereby activating the coagulation system and inducing thrombus formation. Long-term use can easily lead to protein contamination, which can cause pore clogging.

[0004] In order to improve the anticoagulant and anti-fouling properties of polysulfone / polyethersulfone membrane materials, three main methods are used: (1) bulk modification, that is, anticoagulant modification of the polysulfone / polyethersulfone material bulk, and then preparing fiber membrane; (2) surface modification, grafting self-anticoagulant polymers on the fiber surface by chemical methods, photochemical methods or plasma technology, or coating the surface with self-anticoagulant polymers by physical methods; (3) blending modification, forming a spinning solution by blending polysulfone / polyethersulfone with self-anticoagulant functional polymers, and finally spinning into a membrane.

[0005] Polysulfone / polyethersulfone (PS / PES) bulk materials offer stable properties, making modification difficult. Surface grafting and coating modifications are primarily used for small-diameter hollow fiber membranes, hindering large-scale production. Currently, physical blending modification is the primary approach to improving the anticoagulant properties of PS / PES fiber membranes. For example, polyvinylpyrrolidone (PVP), zwitterionic compounds (MPC, a polyphospholipid), and sulfonated functional polymers are incorporated into the PS / PES membrane-forming solution, followed by spinning into membranes. However, during use, the hydrophilic additives in hollow fiber membranes obtained using these modification methods gradually precipitate, resulting in low performance stability. Even when amphiphilic polymers are used, significant phase separation issues persist, which can reduce the strength and mechanical properties of the membranes, and consequently, the membrane's filtration stability. Summary of the Invention

[0006] The object of the present invention is to overcome at least one deficiency of the prior art and to provide a modified polyimide hollow fiber membrane and its application.

[0007] The technical solution adopted by the present invention is:

[0008] In a first aspect, the present invention provides a modified polyimide hollow fiber membrane, wherein the components of the hollow fiber membrane include a polysulfone / polyethersulfone matrix component and a modified polyimide hydrophobic polymer having a matrix component weight content of 30% to 100%, wherein the preparation method of the modified polyimide hydrophobic polymer comprises the following steps:

[0009] 1) Mix water, a strong polar solvent, an alkaline catalyst, and a polyimide resin to form a reaction solvent, and perform a partial hydrolysis reaction at 80 to 120° C. for 5 to 10 hours;

[0010] 2) Cooling the solution from step 1), adjusting the pH to 1-3, and then removing water;

[0011] 3) Adding polyamine to the solution obtained in step 2), stirring and reacting for 2 to 4 hours, and then adding an anticoagulant containing a carboxyl group, and performing a grafting reaction for 12 to 48 hours to obtain the modified polyimide hydrophobic polymer.

[0012] In some examples, the specific composition of the reaction solvent in step 1) is: the mass ratio of water to strong polar solvent is 1:1 to 1:4, the mass fraction of the alkaline catalyst is 5% to 10%, and the mass fraction of the polyimide resin is 20 to 50%.

[0013] In some examples, the alkaline catalyst in step 1) is selected from any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, lithium hydroxide, tetramethylammonium hydroxide, and tetraethylammonium hydroxide; and / or

[0014] The anticoagulant containing a carboxyl group is selected from heparin or a heparin analogue.

[0015] In some examples, the highly polar solvent in step 1) is at least one selected from dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0016] In some examples, the polyamine in step 3) is selected from one or more of ethylenediamine, propylenediamine, tris(2-aminoethyl)amine, and pentaerythritol.

[0017] In some examples, the number average molecular weight of the modified polyimide hydrophobic polymer ranges from 20,000 to 80,000.

[0018] In some examples, the preparation method of the modified polyimide hollow fiber membrane includes the following steps: stirring and dissolving polysulfone / polyethersulfone, modified polyimide hydrophobic polymer, water-soluble porogen and spinning solution solvent at 80-180°C, centrifugally filtering, standing at 40-80°C for 2-24 hours to degas to obtain spinning solution, and the spinning solution is subjected to dry or wet spinning, water washing, stretching and drying to obtain a modified hollow fiber membrane.

[0019] In some examples, the mass ratio of the components in the spinning solution is: 20-60 parts of polysulfone / polyethersulfone, 20-40 parts of modified polyimide hydrophobic polymer, 0.1-10 parts of water-soluble porogen, and 100-300 parts of spinning solution solvent.

[0020] In some instances, the water-soluble porogen is selected from at least one of polyethyleneimine, polyethylene glycol 800, polyethylene glycol 1000, polyethylene glycol 2000, polyvinyl pyrrolidone, polyacrylic acid, polyvinyl alcohol, Tween-20, Tween-60, Tween-80, sodium sorbate, potassium sorbate, sodium citrate, sodium laurate, sodium alginate, sodium lysine, sodium ethylenediaminetetraacetic acid, sodium tetradecanoate, sodium dodecylsulfonate, sodium octanoate, sodium hexanoate, sodium propionate, sodium acetate, sodium oxalate, lithium acetate, sodium chloride, lithium chloride, calcium chloride or copper chloride, and the spinning solution solvent is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide and N,N-dimethylacetamide.

[0021] In a second aspect, the present invention provides an application of the modified polyimide hollow fiber membrane in the preparation of blood purification materials.

[0022] The beneficial effects of the present invention are:

[0023] In some examples of the present invention, polysulfone / polyethersulfone is blended and spun with a modified polyimide hydrophobic polymer grafted with an anticoagulant containing a carboxyl group (such as heparin), and anticoagulant groups are directly obtained on the surface of the hollow fiber membrane, without the need for subsequent anticoagulant modification of the hollow fiber membrane, thereby achieving the purpose of continuous anticoagulant modification; the modified polyimide hydrophobic polymer after grafting is partially hydrolyzed, and the main chain is still polyimide, maintaining obvious hydrophobicity. According to the principle of like dissolves like, the blending effect with polysulfone / polyethersulfone is good, phase separation is not easy to occur, and the performance of the hollow fiber membrane is stable; the modified polyimide hydrophobic polymer after grafting still has a large number of amino groups on the surface after blending, which can further improve the hydrophilic effect of the hollow fiber membrane and improve biocompatibility; polysulfone / polyethersulfone is blended with the grafted modified polyimide hydrophobic polymer to improve the heat resistance of the fiber and the mechanical strength of the fiber. DETAILED DESCRIPTION

[0024] The present invention provides a modified polyimide hollow fiber membrane. The components of the hollow fiber membrane include a polysulfone / polyethersulfone matrix component and a modified polyimide hydrophobic polymer with a matrix component mass content of 30% to 100%. The preparation method of the modified polyimide hydrophobic polymer includes the following steps:

[0025] 1) Mix water, a strong polar solvent, an alkaline catalyst, and a polyimide resin to form a reaction solvent, and perform a partial hydrolysis reaction at 80 to 120° C. for 5 to 10 hours;

[0026] 2) Cooling the solution from step 1), adjusting the pH to 1-3, and then removing water;

[0027] 3) Adding polyamine to the solution obtained in step 2), stirring and reacting for 2 to 4 hours, and then adding an anticoagulant containing a carboxyl group, and performing a grafting reaction for 12 to 48 hours to obtain the modified polyimide hydrophobic polymer.

[0028] The time of the hydrolysis reaction can be adjusted accordingly according to the amount of grafting modification required. Generally speaking, the longer the hydrolysis time, the more complete the hydrolysis, and the more reaction sites can be obtained.

[0029] In some examples, the specific composition of the reaction solvent in step 1) is: the mass ratio of water to strong polar solvent is 1:1 to 1:4, the mass fraction of the alkaline catalyst is 5% to 10%, and the mass fraction of the polyimide resin is 20 to 50%.

[0030] In some examples, the alkaline catalyst in step 1) is selected from any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, lithium hydroxide, tetramethylammonium hydroxide, and tetraethylammonium hydroxide. These bases are easy to remove.

[0031] In some embodiments, the anticoagulant containing a carboxyl group is selected from heparin or a heparin analog. Graft modification can be conveniently achieved using amino groups.

[0032] In some examples, the highly polar solvent in step 1) is at least one selected from dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0033] In some examples, the polyamine in step 3) is selected from one or more of ethylenediamine, propylenediamine, tris(2-aminoethyl)amine, and pentaerythritol.

[0034] In some examples, the number average molecular weight of the modified polyimide hydrophobic polymer ranges from 20,000 to 80,000.

[0035] In some examples, the preparation method of the modified polyimide hollow fiber membrane includes the following steps: stirring and dissolving polysulfone / polyethersulfone, modified polyimide hydrophobic polymer, water-soluble porogen and spinning solution solvent at 80-180°C, centrifugally filtering, standing at 40-80°C for 2-24 hours to degas to obtain spinning solution, and the spinning solution is subjected to dry or wet spinning, water washing, stretching and drying to obtain a modified hollow fiber membrane.

[0036] In some examples, the mass ratio of the components in the spinning solution is: 20-60 parts of polysulfone / polyethersulfone, 20-40 parts of modified polyimide hydrophobic polymer, 0.1-10 parts of water-soluble porogen, and 100-300 parts of spinning solution solvent.

[0037] There are no special requirements for the water-soluble porogen. In some examples, the water-soluble porogen is selected from at least one of polyethylene imine, polyethylene glycol 800, polyethylene glycol 1000, polyethylene glycol 2000, polyvinyl pyrrolidone, polyacrylic acid, polyvinyl alcohol, Tween-20, Tween-60, Tween-80, sodium sorbate, potassium sorbate, sodium citrate, sodium laurate, sodium alginate, sodium lysine, sodium ethylenediaminetetraacetic acid, sodium tetradecanoate, sodium dodecylsulfonate, sodium octanoate, sodium hexanoate, sodium propionate, sodium acetate, sodium oxalate, lithium acetate, sodium chloride, lithium chloride, calcium chloride or copper chloride, and the spinning solution solvent is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide and N,N-dimethylacetamide.

[0038] The following disclosure provides many different embodiments or examples for realizing different solutions of the present invention. In the following examples, unless otherwise specified, all parts are by mass.

[0039] Example 1

[0040] The preparation steps of the modified polyimide hydrophobic polymer of this embodiment are as follows:

[0041] 1) Accurately weigh 20g of water and 80g of N,N-dimethylformamide (DMF) solvent, mix them evenly, add 5g of sodium hydroxide to make a uniform solution, then weigh 20g of polyimide resin and add it to the reaction solvent, and react in a sealed container at 120℃ for 5h;

[0042] 2) Cooling the solution after the reaction in step 1), adding hydrochloric acid to adjust the pH to 1-3, and then removing water by rotary evaporation to obtain a solution with a certain viscosity;

[0043] 3) Add 10 g of ethylenediamine to the solution obtained in step 2) and stir for 2-4 hours to obtain a reaction solution;

[0044] 4) Add 10 mg of heparin to the solution obtained in step 3), stir thoroughly to dissolve, and soak for reaction for 12 hours to obtain a modified polyimide hydrophobic polymer.

[0045] Example 2

[0046] The preparation steps of the modified polyimide hydrophobic polymer of this embodiment are as follows:

[0047] 1) Accurately weigh 25g of water and 75g of N-methyl-2-pyrrolidone, mix well, add 8g of sodium carbonate to prepare a uniform solution, then weigh 30g of polyimide resin and add it to the reaction solvent. React in a sealed container at 100℃ for 5h.

[0048] 2) Cooling the solution after the reaction in step 1), adding hydrochloric acid to adjust the pH to 1-3, and then removing water by rotary evaporation to obtain a solution with a certain viscosity;

[0049] 3) Add 10 g of tris(2-aminoethyl)amine to the solution obtained in step 2) and stir for 2-4 hours to obtain a reaction solution;

[0050] 4) Add 10 mg of heparan sulfate to the solution obtained in step (3), stir thoroughly to dissolve, and soak for reaction for 24 hours to obtain a modified polyimide hydrophobic polymer.

[0051] Example 3

[0052] The preparation steps of the modified polyimide hydrophobic polymer of this embodiment are as follows:

[0053] 1) Accurately weigh 50g of water and 50g of N,N-dimethylacetamide, mix them evenly, add 10g of tetramethylammonium hydroxide to prepare a uniform solution, then weigh 20g of polyimide resin and add it to the reaction solvent. React in a sealed container at 100℃ for 5h.

[0054] 2) Cooling the solution after the reaction in step 1), adding hydrochloric acid to adjust the pH to 1-3, and then removing water by rotary evaporation to obtain a solution with a certain viscosity;

[0055] 3) adding 10 g of pentaerythritol to the solution obtained in step 2) and stirring for 2-4 hours to obtain a reaction solution;

[0056] 4) Add 10 mg of chondroitin sulfate to the solution obtained in step 3), stir thoroughly to dissolve, and soak for reaction for 48 hours to obtain a modified polyimide hydrophobic polymer.

[0057] Preparation of modified hollow fiber membrane

[0058] Table 1

[0059]

[0060] The preparation method of the modified hollow fiber membrane is as follows:

[0061] 1) According to the raw material composition and mass ratio in Table 1 above, the required raw materials were weighed respectively, stirred and dissolved at 100° C. to form a transparent solution, centrifuged and filtered, and allowed to stand at 80° C. for 4 hours to degas to obtain a spinning solution;

[0062] 2) The spinning solution prepared in step 1 is extruded from a spinneret at an extrusion rate of 3-15 mL / min using a spinning device, passed through an air bath of 5-50 cm in air, and then placed in a water bath of 20-50°C for coagulation and molding. The solution is then wound at a speed of 5-50 m / min to form the formed fiber. The formed fiber is immersed in water to remove the residual solvent and unreacted raw materials, and then dried to obtain a hollow fiber membrane.

[0063] Then, performance tests were performed on Examples 4-7 and Comparative Examples 1-2. The test results are shown in Table 2 below:

[0064] Table 2

[0065]

[0066] in conclusion:

[0067] 1) It can be seen that the ultrafiltration coefficient of the hollow fiber membrane prepared by the present invention is not significantly changed compared with the fiber membrane of Comparative Example 1 which has not been hydrophilically modified, and the dialysis performance is not affected;

[0068] 2) The water contact angle is significantly reduced and the hydrophilicity is significantly improved;

[0069] 3) The pure water flux recovery rate after hemodialysis was significantly improved, indicating that the modified hollow fiber membrane reduced the deposition of prothrombin and fibrin;

[0070] 4) APTT (activated partial thromboplastin time) was significantly prolonged, and the anticoagulant effect was significantly improved;

[0071] 5) Compared with hollow fiber membranes modified only with polyvinyl pyrrolidone, its hydrophilicity and anticoagulant effect are also increased to a certain extent.

[0072] Polyimide is the top material in the polymer material pyramid and is the most high-temperature resistant polymer material currently available for practical application. It can be used in the range of 250-350°C, while the operating temperature of polysulfone / polyethersulfone is around 150°C. The temperature resistance of hollow fiber membranes is significantly improved after blending with polyimide. Polyimide also has the highest strength among non-reinforced plastics, with a tensile strength of up to 190MPa, while the tensile strength of polysulfone is only around 80MPa. Therefore, the mechanical properties are also significantly improved after blending.

[0073] The above is a further detailed description of the present invention and should not be considered as a limitation on the specific implementation of the present invention. For those skilled in the art, simple deductions or substitutions that do not depart from the concept of the present invention are within the scope of protection of the present invention.

Claims

1. A modified polyimide hollow fiber membrane, characterized in that: The components of the hollow fiber membrane include a polysulfone / polyethersulfone matrix component and a modified polyimide hydrophobic polymer with a matrix component mass content of 30% to 100%, and the polysulfone / polyethersulfone matrix component and the modified polyimide hydrophobic polymer are composited by blending. The preparation method of the modified polyimide hydrophobic polymer includes the following steps: 1) water, a strong polar solvent, an alkaline catalyst, and a polyimide resin are mixed to form a reaction solvent, and a partial hydrolysis reaction is carried out at 80 to 120° C. for 5 to 10 hours, wherein the strong polar solvent is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide, and the alkaline catalyst is selected from any one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, lithium hydroxide, tetramethylammonium hydroxide, and tetraethylammonium hydroxide; 2) Cooling the solution from step 1), adjusting the pH to 1-3, and then removing water; 3) adding a polyamine to the solution obtained in step 2), stirring and reacting for 2 to 4 hours, and then adding a carboxyl-containing anticoagulant and carrying out a grafting reaction for 12 to 48 hours to obtain the modified polyimide hydrophobic polymer, wherein the polyamine is selected from one or more of ethylenediamine, propylenediamine, tris(2-aminoethyl)amine, and pentaerythritol, and the carboxyl-containing anticoagulant is selected from heparin or a heparin analog.

2. The hollow fiber membrane according to claim 1, characterized in that The specific composition of the reaction solvent in step 1) is as follows: the mass ratio of water to strong polar solvent is 1:1 to 1:4, the mass fraction of the alkaline catalyst is 5% to 10%, and the mass fraction of the polyimide resin is 20 to 50%.

3. The hollow fiber membrane according to claim 1, characterized in that The number average molecular weight of the modified polyimide hydrophobic polymer ranges from 20,000 to 80,000.

4. The hollow fiber membrane according to claim 1, characterized in that The preparation method of the modified polyimide hollow fiber membrane comprises the following steps: stirring and dissolving polysulfone / polyethersulfone, a modified polyimide hydrophobic polymer, a water-soluble porogen and a spinning solution solvent at 80-180° C., centrifugally filtering, standing at 40-80° C. for 2-24 hours to degas to obtain a spinning solution, and dry or wet spinning, washing, stretching and drying the spinning solution to obtain a modified hollow fiber membrane.

5. The hollow fiber membrane according to claim 4, characterized in that The mass ratio of the components in the spinning solution is: 20-60 parts of polysulfone / polyethersulfone, 20-40 parts of modified polyimide hydrophobic polymer, 0.1-10 parts of water-soluble porogen, and 100-300 parts of spinning solution solvent.

6. The hollow fiber membrane according to claim 4 or 5, characterized in that The water-soluble porogen is selected from at least one of polyethylene imine, polyethylene glycol 800, polyethylene glycol 1000, polyethylene glycol 2000, polyvinyl pyrrolidone, polyacrylic acid, polyvinyl alcohol, Tween-20, Tween-60, Tween-80, sodium sorbate, potassium sorbate, sodium citrate, sodium laurate, sodium alginate, sodium lysine, sodium ethylenediaminetetraacetic acid, sodium tetradecanoate, sodium dodecylsulfonate, sodium octanoate, sodium hexanoate, sodium propionate, sodium acetate, sodium oxalate, lithium acetate, sodium chloride, lithium chloride, calcium chloride or copper chloride, and the spinning solution solvent is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide and N,N-dimethylacetamide.

7. Use of the modified polyimide hollow fiber membrane according to any one of claims 1 to 6 in the preparation of blood purification materials.

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